The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study

Abstract

ObjectiveTo assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes.MethodsThis multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6–24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected.ResultsBaseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low.ConclusionADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA.Trial registrationThis study was registered on www.ClinicalTrials.gov (NCT01981473).

Phase III randomized study of the proposed adalimumab biosimilar GP2017 in psoriasis: impact of multiple switches

“…Concerns have been raised regarding differences in the incidence or type of AEs, as well as the potential for increased immunogenicity leading to hypersensitivity reactions and/or decreased effectiveness . This may be of particular concern for adalimumab, which has higher intrinsic immunogenicity than other anti‐tumour necrosis factor molecules . Generation of data, either in real‐world situations or in clinical trials assessing the impact of multiple switches between a reference medicine and biosimilar, would be beneficial to address these concerns.…”

“…2,3 This may be of particular concern for adalimumab, which has higher intrinsic immunogenicity than other anti-tumour necrosis factor molecules. [20][21][22] Generation of data, either in real-world situations or in clinical trials assessing the impact of multiple switches between a reference medicine and biosimilar, would be beneficial to address these concerns. These data will reassure clinicians when prescribing biosimilars, and help to address fears that multiple switching between reference medicines and their biosimilars may have negative consequences.…”

“…This was a randomized, multicentre phase III confirmatory study consisting of four periods: screening, treatment period 1 (TP1, randomization to week 17), treatment period 2 (TP2, weeks [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and an extension period (weeks 35-51) ( Fig. 1).…”

Application of nSMOL coupled with LC‐MS bioanalysis for monitoring the Fc‐fusion biopharmaceuticals Etanercept and Abatacept in human serum

“…All biologics and Fc‐fusion molecules are proteins, and therefore, intrinsically possess immunogenic potentials for B‐cell and T‐cell epitopes. Since therapy against IMIDs requires a long‐term and repeated administration for clinical efficacy, there is a constant potential to produce antidrug antibodies (ADA) . The existence of ADAs in patient circulation is considered to be one of the possibilities for the decreased levels of protein pharmaceuticals in blood, the loss of efficacy, or drug‐related adverse events.…”

Low prevalence of anti‐xenobiotic antibodies among the occupationally exposed individuals is associated with a high risk of cancer

“…The anti‐xenobiotic Abs bind to xenobiotics, and these antibodies can block cancer provoking property of xenobiotics. Formation of immune complexes between xenobiotics and anti‐xenobiotic Abs helps in increasing the clearance of xenobiotics from the body …”